1. Field of the Invention
The present invention relates generally to analyzing time series data, and more specifically, to non-invasively assessing therapeutic toxicity and efficacy from physiologic measurements.
2. Related Art
The physiologic systems of a living organism generate complex fluctuations in their output signals. The complex fluctuations (also referred to as “complexity”) arise from the interaction of a myriad of structural units and regulatory feedback loops that operate over a wide range of temporal and spatial scales. This interaction reflects the organism's ability to adapt to the stress of everyday life.
Being able to quantify or model physiologic complexity would provide insight into the underlying dynamics of an organism. For example, a decrease in physiologic complexity can be symptomatic of a pathologic process. However, contemporary mathematical approaches to measuring the complexity of biological signals fail to account for the multiple time scales inherent in such time series. These approaches have yielded contradictory findings when applied to real-world datasets obtained in health and disease states.
Conventional biomedical approaches to designing therapeutic interventions for pathologic processes are also plagued with several shortcomings. Current screening tests and assays for the efficacy and toxicity of pharmacologic and non-pharmacologic interventions are based primarily on local effects and on the measurement of a limited range of markers. Such measures fail to account for systemic effects associated with integrative feedback (also referred to as a “systems biology approach”). Thus, a drug might appear to have beneficial effects in the short-term, or based on site-specific actions. However, more sustained use might be associated with lethal toxicities not detected in the conventional evaluation. The literature is replete with examples of such unexpected toxicities, including the notorious examples of cardiac “antiarrhythmic” drugs that have “proarrhythmic” effects and increase the risk of sudden cardiac arrest.
A fundamental problem in the development of novel therapeutic agents and the ongoing monitoring of approved drugs, as well as non-pharmacologic interventions, is the sensitive assessment of their systemic safety and efficacy. Current methodologies for evaluating both efficacy and toxicity, however, largely fail to account for the effects on integrative physiologic function.
Therefore, a need exists to develop a technology that can overcome the aforementioned limitations and provide a more efficient and cost-effective technique and/or methodology for evaluating complexity and/or therapeutic interventions.